Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity.

Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-specific T cells in women who were pregnant with a male fetus. Fetal-specific CD8(+) T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy and that unlike reports from some murine models, fetal-specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-related complications.

Birth order and ratio of brothers to sisters in transsexuals.

BACKGROUND: As previous studies with homosexual males have revealed a later birth order, more older brothers and more brothers than sisters, this research was extended to a large series of transsexual males and females, some of whom are homosexual. METHODS: The male sample comprised 442 male-to-female transsexuals, subdivided by sexual partner preference: 106 homosexual, 135 heterosexual, 155 bisexual and 46 asexual. One hundred female-to-male transsexuals were also studied: 75 homosexual, 16 bisexual, seven heterosexual and five asexual. Birth order was computed by both Slater's Index and Berglin's Index. RESULTS: Homosexual male-to-female transsexuals have a later than expected birth order and more older brothers than other subgroups of male-to-female transsexuals. Each older brother increases the odds that a male transsexual is homosexual by 40 %. CONCLUSIONS: Hypotheses explaining the extension of prior findings to this large sample of transsexual males include a progressive maternal immunization to the male foetus either through the H-Y antigen or protein-bound testosterone or alterations in foetal androgen levels in successive pregnancies, all modifying male psychosexual development. Data on the sexual orientation of younger brothers of homosexual male transsexuals in this study are not consistent with the progressive immunization hypothesis.

Evidence that the Gya, Hy and Joa antigens belong to the Dombrock blood group system.

Ten red cell samples lacking the high incidence Gya antigen were found to have the previously undescribed Do(a-b-) phenotype. Fifteen Hy- red cell samples were Do(a-b+) with weak expression of Dob and 6 Jo(a-) red cell samples were Do(a+) with weak expression of Doa. Five of the 6 Jo(a-) samples had extremely weak expression of Dob. The sixth Jo(a-) was Do(b-). Immune precipitates were prepared from radio-iodinated antigen-positive red cells with anti-Gya, -Hy, -Doa and Dob. Immunoblotting of these immune precipitates with affinity-purified anti-Gya and anti-Dob under non-reducing conditions revealed similar broadly migrating bands of M(r) 48,700-59,750, suggesting that the Doa and Dob antigens are carried on the same glycoprotein as Gya and Hy. The phenotypically associated high incidence Joa antigen has previously been shown to reside on the Gya/Hy glycoprotein. Enzyme-treated and chemically modified red cells tested with anti-Doa, -Dob, -Gya, -Hy and -Joa gave the same pattern of reactivity. We propose that Gya, Hy and Joa become part of the Dombrock blood group system and that, henceforth, the Gya/Hy-active glycoprotein be renamed the Dombrock-active glycoprotein. The Gy(a)-Hy- Jo(a-) phenotype constitutes the 'null' phenotype within the Dombrock system.

On the expression of H-Y antigen in transsexuals.

Histocompatibility-Y (H-Y) antigen, the presumptive inducer of the mammalian testis, is present in the cells of normal males and not in the cells of normal females. Recent reports have implied that patients with transsexualism exhibit H-Y antigen phenotypes at variance with those of normal males and females and, thus, that H-Y serology might provide a tool for the diagnosis and study of the transsexual condition. We therefore evaluated blood and testicular cells from 21 male-to-female transsexuals using conventional and monoclonal H-Y antibodies. We found no evidence of abnormal H-Y phenotype. Five of the patients were interviewed postoperatively by two examiners and rated for the diagnosis of transsexualism. Three of the five were rated primary transsexual by one or both examiners, and two were rated secondary transsexual.